The Studies of the Ocular Complications of AIDS Research Group is dedicated to understanding and improving the outcomes of the ocular complications of AIDS. The Longitudinal Study of the Ocular Complications of AIDS (LSOCA) is a prospective cohort study of these complications and their outcomes in the era of highly active antiretroviral therapy (HAART), and is currently in its ninth year of follow-up. Unlike most cohort studies of HIV-infected patients, which enroll from selected risk groups, LSOCA enrolls patients with AIDS from all risk groups. As of 31 December 2006 the LSOCA cohort has recruited 2024 patients, of whom 448 have cytomegalovirus retinitis and 18 have other ocular opportunistic infections (Ols). Although HAART has decreased the incidence of ocular Ols among patients with AIDS, new cases continue to occur, and there is an increasingly large number of patients with AIDS and ocular Ols who have experienced immune recovery. Although short-term outcomes have been described, no long-term data are available, and the durability of the response to HAART among these patients is unknown. Long-term data are critical for assessing resource needs and determining management guidelines. There also are abnormalities of the visual system among patients with AIDS without ocular Ols,manifested as decreased contrast sensitivity, often of sufficient magnitude to impair reading speed, and as visual field loss. Little is known about the pathogenesis of, the risk factors for, and the course of this neuroretinal disorder, particularly its long-term consequences. In addition, there appears to be an increased prevalence of cataract among patients with AIDS without ocular Ols,which may be aggravated by the metabolic side effects of HAART, such as diabetes and hyperlipidemia. Host genetic factors have a substantial effect on the course of HIV infection, but their effect on the incidence and course of ocular complications is unknown. The immunologic mechanisms underlying ocular complications also need to be elucidated better. The LSOCA cohort will address the ongoing need for long-term data in these areas. The specific aims of this proposal are to evaluate the following among patients with AIDS: 1) the long-term outcomes of ocular Ols;2) visual impairment among patients without ocular Ols;and 3) host genetic risk factors for and immunologic mechanisms of ocular complications and their outcomes.